This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.
The treatment of osteoarthritis (OA), a degenerative joint disease affecting more than 40% of U.S. adults and an economic burden annually exceeding $65 billion, is an unmet need in medicine. A hallmark of OA is the progressive wear of articular cartilage, the primary joint bearing material that facilitates smooth, pain-free movement. The treatment of cartilage/bone (osteochondral) defects, leading to OA in the long term, is challenging because the tissue is intrinsically recalcitrant to repair, partly due to its avascularity and slow cellular turnover. Moreover, cartilage has a stratified (zonal) structure with spatial gradients in collagen alignment and localized protein expression. In recent years, Tissue engineering-based methods have shown promise to repair defects, but none is able to recapitulate the native structure of cartilage, and the typical end-point for diseased tissue is biomechanically-inferior fibrous repair tissue and/or total joint arthroplasty.
Collagen, the main structural protein found in the connective tissue of animals, can be aligned using a variety of techniques. Scaffolds with isotropically-oriented fibrils exhibit poor mechanical strength in specific and functionally-important directions. Anisotropic collagen scaffolds closely resemble the natural articular cartilage environment and promote cellular migration and growth, possibly due to alignment of focal adhesions and haptotaxis. Drainage-induced orientation is a process by which collagen solution is precipitated into bundles and placed on an inclined surface to align the fibers. The stretch-induced orientation method involves a fluid absorption process that contracts collagen. Both these methods have very low reproducibility with nonuniform fibril orientation. Electrospinning uses electrical fields to produce oriented collagen fibers. This technology has shown promise for creating continuous two dimensional fibers useful for skin and tendon regeneration, however this process also denatures collagen. A separate electrochemical process attains high degree of two dimensional collagen fiber orientation for tendon/ligament replacement. This process is carried out in distilled water and requires low electric voltage and current. However, it is unclear whether electrospinning and electrochemical processes are capable of creating complex three-dimensional and zonal architecture required for osteochondral scaffolds.
Existing scaffolds do not have zonal collagen alignment that match the osteochondral structure of cartilage and bone. Additionally, existing collagen-derived scaffolds exhibit an inferior mechanical stiffness, and are thus unsuitable for long-term repair success.
The repair and regeneration of articular cartilage is challenging. Unfortunately, there is no product or surgical strategy that results in reproducibly healthy tissue. Several traditional techniques of cartilage repair are based on accessing the subchondral vascularity and marrow by drilling of the subchondral bone, spongialization, or microfracturing. A common result of these techniques is a fibrocartilage-like repair tissue developed with inferior composition, structure, and mechanical properties compared to normal cartilage.
Autologous chondrocyte transplantation (ACT) is a current “gold standard” of practice for the repair of deep cartilage defects. ACT involves the reintroduction of expanded autologous cells into a surface defect, although results are highly variable.
Therefore, there is a need for the ability to engineer complex and native zonal structure of cartilage and bone in order to restore depth-dependent properties and normal mechanical function.